Pentose Phosphate Pathway

Overview

• Importance: Essential for synthesis reactions (neurotransmitters, lipids, cholesterol, nucleotides)
• Role in Free Radical Reactions: Important for combating oxidative stress

Initial Steps

1. Glucose Entry:
   • Transported into the liver cell via GLUT2 transporters
   • Phosphorylated by glucokinase to form glucose-6-phosphate (G6P)
   • ATP is converted to ADP in this phosphorylation step
2. Glycolysis Pathway: G6P can enter glycolysis to eventually form pyruvate, generating a net of 2 ATP
3. Pentose Phosphate Pathway (PPP):
   • G6P can also enter the PPP, crucial for synthesizing various molecules and defense against oxidative stress

Pentose Phosphate Pathway (PPP)

• Phases: Oxidative and Non-oxidative

Oxidative Phase

1. G6P to 6-Phosphoglucono-δ-lactone
   • Enzyme: Glucose-6-phosphate dehydrogenase (G6PD)
   • NADP+ is reduced to NADPH
2. 6-Phosphoglucono-δ-lactone to 6-Phosphogluconate
   • Enzyme: Lactonase
   • Simple hydrolysis reaction
3. 6-Phosphogluconate to Ribulose-5-Phosphate (Ru5P)
   • Enzyme: 6-Phosphogluconate dehydrogenase
   • NADP+ is reduced to NADPH, and CO2 is released

Non-Oxidative Phase

1. Ru5P to Ribose-5-Phosphate (R5P) and Xylulose-5-Phosphate (X5P)
   • Enzymes: Isomerase and Epimerase respectively
2. Conversion and Shuffling of Carbons:
   • R5P and X5P react with Transketolase (requires Thiamine Pyrophosphate, TPP) to form Glyceraldehyde-3-Phosphate (G3P) and Sedoheptulose-7-Phosphate (S7P)
   • G3P and S7P react via Transaldolase to form Fructose-6-Phosphate (F6P) and Erythrose-4-Phosphate (E4P)
   • E4P and another X5P react with another Transketolase to form another G3P and F6P
   • Resulting molecules can enter glycolysis or gluconeogenesis depending on the cell's needs

Key Products and Functions

1. NADPH
   • Reducing agent in biosynthetic reactions: fatty acid synthesis, cholesterol synthesis, nucleotide synthesis
   • Important for anti-oxidative defense (e.g., regenerating reduced glutathione)
2. R5P
   • Synthesis of nucleotides and nucleic acids (DNA, RNA, ATP, NAD+, FAD, Coenzyme A)

Importance of Pathway

• Biosynthetic Roles: lipid, cholesterol, and nucleotide synthesis
• Antioxidant Defense: NADPH helps regenerate antioxidants (e.g., glutathione)
• Intermediates Shuffling: Flexible use of intermediates for making other molecules (e.g., glycolytic intermediates)
• Regulation and Disorders: Deficiency in G6PD can lead to hemolytic anemia with Heinz body formation

Conclusion

• Oxidative Phase: Generates NADPH and R5P
• Non-Oxidative Phase: Interconverts sugar phosphates useful in various metabolic pathways
• Next Focus: Regulation and specific biochemical implications

Remember: This pathway is crucial for both synthesis and defense in cells. Stay tuned for the next video focused on regulation!